Destruction of cytochrome P-450 by vinyl fluoride, fluroxene, and acetylene. Evidence for a radical intermediate in olefin oxidation

Biochemistry ◽  
1982 ◽  
Vol 21 (6) ◽  
pp. 1331-1339 ◽  
Author(s):  
Paul R. Ortiz de Montellano ◽  
Kent L. Kunze ◽  
Hal S. Beilan ◽  
Conrad Wheeler
Keyword(s):  
Radical Intermediate ◽  
Olefin Oxidation ◽  
Vinyl Fluoride ◽  
Cytochrome P 450

scholarly journals Acetylene, a mammalian metabolite of 1,1,1-trichloroethane

1992 ◽  
Vol 286 (2) ◽  
pp. 353-356 ◽  
Author(s):  
H Dürk ◽  
J L Poyer ◽  
C Klessen ◽  
H Frank
Keyword(s):  
Acute Toxicity ◽  
Rat Liver ◽  
Trichloroacetic Acid ◽  
Spin Trapping ◽  
Radical Intermediate ◽  
Cytochrome P 450

1,1,1-Trichloroethane (TCE) is a widely used industrial solvent of low acute toxicity. It is slowly oxidized to trichloroethanol and trichloroacetic acid by cytochrome P-450-dependent mono-oxygenases. Increased inhalative uptake by rats under hypoxia and spin-trapping experiments indicate that TCE is also reductively metabolized to a radical intermediate. Acetylene is formed as a metabolite, suggesting transfer of an additional electron to form the corresponding carbene. Hypoxia and induction of mixed-function mono-oxygenases accelerate the formation of acetylene. Experiments performed in vitro with rat liver microsomal fractions yield analogous results.

Ultrastructure and Drug Metabolism in the Developing Guinea Pig

1973 ◽  
Vol 31 ◽  
pp. 538-539
Author(s):  
W. Kuenzig ◽  
M. Boublik ◽  
J.J. Kamm ◽  
J.J. Burns
Keyword(s):  
Guinea Pig ◽  
Metabolic Activity ◽  
Animal Species ◽  
Adult Animal ◽  
Smooth Endoplasmic Reticulum ◽  
Fetal Life ◽  
Mixed Function Oxidase ◽  
Cytochrome P 450 ◽  
Microsomal Mixed Function Oxidase ◽  
Mixed Function Oxidase Activity

Unlike a variety of other animal species, such as the rabbit, mouse or rat, the guinea pig has a relatively long gestation period and is a more fully developed animal at birth. Kuenzig et al. reported that drug metabolic activity which increases very slowly during fetal life, increases rapidly after birth. Hepatocytes of a 3-day old neonate metabolize drugs and reduce cytochrome P-450 at a rate comparable to that observed in the adult animal. Moreover the administration of drugs like phenobarbital to pregnant guinea pigs increases the microsomal mixed function oxidase activity already in the fetus.Drug metabolic activity is, generally, localized within the smooth endoplasmic reticulum (SER) of the hepatocyte.

Polymorphism of p-450 cytochrome detoxication genes in adolescents depending on the degree of contamination of the organism by heavy metals

2020 ◽  
Vol 99 (5) ◽  
pp. 478-482
Author(s):  
N. P. Setko ◽  
A. G. Setko ◽  
Ekaterina V. Bulycheva ◽  
A. V. Tyurin ◽  
E. Yu. Kalinina
Keyword(s):  
Heavy Metals ◽  
Environmental Factors ◽  
Heavy Metal Contamination ◽  
Atomic Absorption Spectrophotometry ◽  
The Body ◽  
Lead And Cadmium ◽  
Cyp2b6 Gene ◽  
Cytochrome P 450 ◽  
Gene Cyp1a1 ◽  
Group 1

Introduction. Changes in the body of children and adolescents aimed at adapting to environmental factors are determined by genetic polymorphism in xenobiotic biotransformation genes, determining the degree of susceptibility of the child’s body to pollutants, which is the basis of modern personalized preventive medicine when managing risks to the health of the child population under the influence of environmental factors. Material and methods. Trace elements, including heavy metals, lead and cadmium, were determined in the hair of 256 practically healthy teenagers by atomic absorption spectrophotometry. Depending on the level of content of the latter, two groups of adolescents were formed to determine six genes of the cytochrome P-450 family. Group 1 consisted of adolescents whose cadmium lead content exceeded the average Russian indices. The second group included adolescents whose heavy metals were above the level of average Russian standards. Results. Studies have shown that in adolescents of the 1st group, compared with the data of adolescents of the 2nd group, an increase in the number of carriers of two mutant alleles at the locus rs 1048943 (gene CYP1A1) is 3.08 times, rs 464621 (gene CYP1A1) is 1. 8 times; locus rs 2069522 (CYP1A2 gene) 3.63 times; locus rs 1799853 (CYP2C9 * 2 gene) 4.5 times; locus rs 1057910 (gene CYP2C9 * 3) 3.8 times and locus rs 2279343 (gene CYP2B6) 4.25 times. Moreover, carriers of two normal alleles in adolescents of the first group at the locus rs 1048943 (gene CYP1A1) were 5.14 times; locus rs 2279343 (CYP2B6 gene) was 6.5 fold less than among adolescents of the 2nd group; and at the locus rs 464621 (gene CYP1A1), rs 2069522 (gene CYP1A2), rs 1799853 (gene CYP2C9 * 2), rs 1057910 (gene CYP2C9 * 3) there were no carriers of normal homozygotes. Conclusion. Group 1 adolescents with heavy metal contamination of the body are carriers significantly in a greater number of pathological mutations in the genes of the cytochrome P-450 detoxification system in comparison with data from group 2 adolescents.

Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis

1984 ◽  
Vol 107 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Itaru Kojima ◽  
Etsuro Ogata ◽  
Hiroshi Inano ◽  
Bun-ichi Tamaoki
Keyword(s):  
Carbon Monoxide ◽  
Hydroxysteroid Dehydrogenase ◽  
Dependent Manner ◽  
In Vitro Production ◽  
Mitochondrial Preparation ◽  
Final Reaction ◽  
Vitro Production ◽  
Dose Dependent ◽  
Cytochrome P 450

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.

Radical Enzymes Control the Chemistry of Their Highly Reactive Intermediates Using the Quantum Coulombic Effect

2020 ◽  
Author(s):  
Hossein Khalilian ◽  
Gino A. DiLabio
Keyword(s):  
Hydrogen Bonding ◽  
Molecular Orbital ◽  
Reactive Intermediates ◽  
Hydrogen Bonding Interaction ◽  
Orbital Ordering ◽  
Dynamic Nature ◽  
Radical Intermediate ◽  
Highest Occupied Molecular Orbital ◽  
Bonding Interaction ◽  
Close Proximity

Here, we report an exquisite strategy that the B12 enzymes exploit to manipulate the reactivity of their radical intermediate (Adenosyl radical). Based on the quantum-mechanic calculations, these enzymes utilize a little known long-ranged through space quantum Coulombic effect (QCE). The QCE causes the radical to acquire an electronic structure that contradicts the Aufbau Principle: The singly-occupied molecular orbital (SOMO) is no longer the highest-occupied molecular orbital (HOMO) and the radical is unable to react with neighbouring substrates. The dynamic nature of the enzyme and its structure is expected to be such that the reactivity of the radical is not restored until it is moved into close proximity of the target substrate. We found that the hydrogen bonding interaction between the nearby conserved glutamate residue and the ribose ring of Adenosyl radical plays a crucial role in manipulating the orbital ordering

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